In the case of many pharmaceuticals, injectable solutions or suspensions formed from them have insufficient stability to allow for prolonged storage prior to use, although the product prior to solution, dilution or suspension may have adequate stability. Preparation of the injectable product at the time of use from two components presents various problems in that it is time consuming, requires additional apparatus, and is prone to error and loss of sterility; there is therefore a demand for disposable prefilled syringe systems permitting the components to be readily mixed within the system at the time of use, in predetermined proportions and with the maintenance of sterile conditions.
A number of such systems have been proposed, but to the best of applicant's knowledge, none has received widespread acceptance. In a first type of system, the plunger of a first syringe, the barrel of which contains a first component of an injectable medicament and is provided with means for mounting a hypodermic needle, is formed by a second concentric syringe, the barrel of which contains a fluid second component of the medicament, and which is provided, in place of a hypodermic needle with some form of non-return valve. In use, a plunger of the second syringe is pressed into the barrel of the latter to expel its contents through the non-return valve into the first syringe, whereafter the second syringe may be used as the plunger of the first syringe to expel the now mixed contents of the latter through a hypodermic needle attached to the first barrel. The weak point of this arrangement is the non-return valve, which must positively separate the two components during storage, yet open readily during use. In practice, it is desirable that the component be positively sealed apart during storage, and any system which relies solely on a pressure differential operated non-return valve cannot provide such a positive seal. Examples of such systems are discussed for example in U.S. Pat. Nos. 3,659,749 (Schwartz), 3,678,931 and 3,682,174 (Cohen), 3,685,514 (Cheney), 4,405,317 (Case) and 4,464,174 (Ennis), and the multiplicity of valve designs disclosed and discussed in these patents is illustrative that the existence of problems associated with design of a suitable non-return valve is well appreciated in the art.
In another type of system, a single barrel and plunger are employed, and the components are separated within the barrel by a sliding seal system having portions relatively movable under the influence of differential pressures such that a needle incorporated in the sliding seal systems ruptures the seal provided by the system so as to permit the plunger to force a liquid component through the needle into admixture with the other component prior to injection. Very careful design is obviously necessary to provide the correct differential pressures and degrees of flexibility and frictional engagement between the parts if correct operation is to be assured, and the overall length of the system is comparatively large. Separation between the components relies on a sliding plug or plugs. Examples of such systems are shown in U.S. Pat. Nos. 4,055,177 (Cohen) and 4,059,109 (Tischlinger). In both the above discussed types of syringe, the entire contents of both components must be mixed before use of the syringe.
U.S. Pat. No. 4,060,082 (Lindberg et al) shows a system which consists in effect of two syringes connected in tandem by a collapsible sleeve. By collapsing the sleeve, the contents of a second of the syringes may be injected through a soft rubber head of a first of the syringes. The second syringe is then removed, and a plunger shaft is attached to the plunger head of the first syringe to ready it for administration of the mixed medicament. This system provides improved separation of the components, and can readily be adapted to provide different quantities and proportions of the components, but has a very great overall length (see FIG. 1) and requires a fair amount of manipulation to ready it for use. In common with a number of other systems discussed, the interior volume of the system is substantially increased by the space which must be allowed for displacement of one of the components past a valve or seal without setting up back pressures which will prevent proper operation.
U.S. Pat. No. 4,166,240 (Guiney) discloses an arrangement in which one component of the medicament is stored in a compartment in the plunger of the syringe, from which it may be released in various ways to ready the syringe for use. Clearly the size of the compartment is restricted, and again it is not clear that a positive seal is provided between the compartments.
U.S. Pat. No. 3,659,769 (Schwartz), already mentioned above, differs from other patents in its group in that, rather than being formed in effect by two concentric syringes, the inner of which is discharged into the outer prior to injecting the contents of the latter, only a single syringe is utilized with a hollow plunger which contains a liquid component drawn into admixture with a powder component into the syringe barrel by a vacuum set up by withdrawal of the plunger from the barrel. This arrangement has the advantage of compactness, but is critically dependent for its functionality upon the proper operation of the plunger head, which provides a non-return valving function. Certain embodiments provide an additional seal between the components during storage, but breakage or removal of this seal is also critically dependent upon maintenance of a proper degree of frictional engagement between the parts. For example, in the FIGS. 1-4 embodiment, breakage of the end 42 depends upon the plunger 30 being rotatable in the piston without the piston rotating in the syringe barrel.
U.S. Pat. No. 4,313,440 (Ashley) shows a further centric syringe arrangement, in which an inner syringe has a needle which penetrates the plunger head of an outer syringe and enters a needle of that outer syringe. This device is intended for a number of special purposes in which different liquids are to be injected into and/or withdrawn from a patient, and is not a mixing syringe in the same sense as the other patents considered.